Method and system for endotracheal/esophageal stimulation prior to and during a medical procedure

ABSTRACT

A method of performing a medical procedure, such as surgery, is provided. A nerve is stimulated in order to adjust the beating of the heart to a first condition, such as a stopped or slowed condition. The medical procedure is performed on the heart or another organ. The stimulation of the nerve is stopped in order to adjust the beating of the heart to a second condition, such as a beating condition. The heart itself may also be stimulated to a beating condition, such as by pacing. The stimulation of the nerve may be continued in order to allow the medical procedure to be continued. Systems and devices for performing the medical procedure are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of application Ser.No. 09/670,369, Sep. 26, 2000, to inventors Hill et al., saidapplication Ser. No. 09/670,369 is a continuation-in-part of applicationSer. No. 09/433,323, Nov. 3,1999, to inventors Hill and Jonkman, saidapplication Ser. No. 09/433,323 is a continuation of application Ser.No. 09/070,506, Apr. 30, 1998, Pat. No. 6,006,134, to inventors Hill andJonkman, said application Ser. No. 09/070,506 is a continuation-in-partof application Ser. No. 08/640,013, Apr. 30, 1996, now abandoned.

FIELD OF THE INVENTION

[0002] This invention relates to methods for performing a medicalprocedure, especially a procedure during which it is necessary to adjustthe beating of the heart. More particularly, this invention relates tomethods and systems of stimulating a nerve in order to modify thebeating of a heart to allow a medical procedure to be performed or forblood flow to be controlled.

BACKGROUND OF THE INVENTION

[0003] The current leading cause of death in the United States iscoronary artery disease in which the coronary arteries are blocked byatherosclerotic plaques or deposits of fat. The typical treatment torelieve a partially or fully blocked coronary artery is coronary arterybypass graph (CABG) surgery.

[0004] CABG surgery, also known as “heart bypass” surgery, generallyentails using a graph to bypass the coronary obstruction. The procedureis generally lengthy, traumatic and subject to patient risks. Among therisk factors involved is the use of a cardiopulmonary bypass (CPB)circuit, also known as a “heart-lung machine,” to pump blood andoxygenate the blood so that the patient's heart may be stopped duringthe surgery.

[0005] Conventional CABG procedures are typically conducted on a stoppedheart while the patient is on a (CPB) circuit. A stopped heart and a CPBcircuit enables a surgeon to work in a bloodless, still operative field.However, there are a number of problems associated with CABG proceduresperformed while on CPB including the initiation of a systemicinflammatory response due to interactions of blood elements with theartificial material surfaces of the CPB circuit and global myocardialischemia due to cardioplegic cardiac arrest. For these reasons, avoidingthe use of CPB or cardioplegic cardiac arrest may help minimizepost-operative complications.

[0006] One method, as disclosed in U.S. Pat. No. 5,651,378 to inventorsMatheny and Taylor and in U.S. Pat. No. 5,913,876 to inventors Taylor etal., for facilitating coronary bypass surgery on a beating heart andthereby avoid the use of CPB and cardioplegic cardiac arrest includesstimulating the vagal nerve electrically in order to temporarily stop orsubstantially reduce the beating of the heart. This may be followed bypacing the heart to start its beating.

[0007] Another method, as disclosed in two published PCT applications,WO 99/09971 and WO 99/09973, both to inventor Puskas, involves stoppingthe beating of the heart during coronary bypass surgery using electricalstimulation of the vagal nerve in combination with administration ofdrugs. Another method, as disclosed in U.S. Pat. No. 6,060,454 toinventor Duhaylongsod, involves stopping the beating of the heart duringcoronary bypass surgery via the local delivery of drugs to the heart.

[0008] Although it is desirable to stop the heart for a period of timein order to allow the surgeon to accomplish a required task withoutinterference from heart movement, i.e. a motionless operative field, itis undesirable to have the heart stopped for too long a period of timesince the body needs, among other things, a constant supply of oxygen.In fact, it is particularly important to maintain sufficient blood flow,and therefore oxygen flow, to the brain. Stopping the heart forprolonged periods of time may cause damage to the patient.

[0009] It is thus important to be able to precisely control andcoordinate the amount and duration of stimulation to the vagal nerve andthe heart. One type of electrode arrangement that allows such precisecontrol is an electrode tube which is suitable for insertion into apatient's trachea or esophagus. This arrangement provides aconfiguration of electrodes which can not only stimulate a variety ofnerve fibers but may also be configured to stimulate the patient'sheart, ventilate the patient's lungs and/or control pain duringstimulation. This electrode arrangement also allows for sensing ormonitoring of various physiological processes.

[0010] It would be desirable therefore to provide a method forcontrollably stopping or slowing the heart intermittently for diagnosticand therapeutic purposes.

[0011] Additionally, it would be desirable to provide a method forcontrollably stopping or slowing the heart intermittently in order tocontrol blood flow.

[0012] Additionally, it would be desirable to provide a method forcontrollably stopping or slowing the heart intermittently in order toperform a medical procedure on the heart or another organ.

[0013] Additionally, it would be desirable to provide a means forcoordinating stimulation of the heart and other body components.

[0014] Additionally, it would be desirable to provide a means forevaluating the stimulation output from a variety of electrodes todetermine the best stimulation configuration.

SUMMARY OF THE INVENTION

[0015] One aspect of the present invention provides a method forevaluating stimulation during a medical procedure. A site is stimulatedwith a first electrode arrangement. The stimulation at the site is thenevaluated to provide a first stimulation value. The first electrodearrangement may comprise one or more electrodes such as nervestimulation electrodes, endotracheal electrodes, endoesophagealelectrodes, intravascular electrodes, transcutaneous electrodes,intracutaneous electrodes, balloon-type electrodes, basket-typeelectrodes, umbrella-type electrodes, tape-type electrodes, suction-typeelectrodes, screw-type electrodes, barb-type electrodes, bipolarelectrodes, monopolar electrodes, metal electrodes, wire electrodes,patch electrodes, cuff electrodes, clip electrodes, needle electrodes,probe electrodes, cardiac stimulation electrodes, pacing electrodes andepicardial electrodes.

[0016] The method may also involve stimulating the site with asubsequent electrode arrangement and evaluating stimulation to provide asubsequent stimulation value. The first stimulation and subsequentstimulation values may be continued with the electrode arrangementassociated with the best stimulation value. The subsequent electrodearrangement may comprise one or more electrodes such as nervestimulation electrodes, endotracheal electrodes, endoesophagealelectrodes, intravascular electrodes, transcutaneous electrodes,intracutaneous electrodes, balloon-type electrodes, basket-typeelectrodes, umbrella-type electrodes, tape-type electrodes, suction-typeelectrodes, screw-type electrodes, barb-type electrodes, bipolarelectrodes, monopolar electrodes, metal electrodes, wire electrodes,patch electrodes, cuff electrodes, clip electrodes, needle electrodes,probe electrodes, cardiac stimulation electrodes, pacing electrodes andepicardial electrodes.

[0017] Another aspect of the present invention provides a method ofperforming a medical procedure. A nerve is stimulated with a firstelectrode arrangement to adjust the beating of a heart to a firstcondition. Stimulation is evaluated from the first electrode arrangementto provide a first stimulation value. The nerve is then stimulated witha subsequent electrode arrangement and stimulation is evaluated from thesubsequent electrode arrangement to provide a subsequent stimulationvalue. A desired electrode arrangement is selected based on the firststimulation value and the subsequent stimulation value and the nerve isstimulated with the desired electrode arrangement. The first and thesubsequent electrode arrangements may comprise one or more electrodessuch as nerve stimulation electrodes, endotracheal electrodes,endoesophageal electrodes, intravascular electrodes, transcutaneouselectrodes, intracutaneous electrodes, balloon-type electrodes,basket-type electrodes, umbrella-type electrodes, tape-type electrodes,suction-type electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, patch electrodes, cuff electrodes, clip electrodes, needleelectrodes, probe electrodes, cardiac stimulation electrodes, pacingelectrodes and epicardial electrodes.

[0018] The medical procedure may be performed on an organ. Stimulationof the nerve may then be reduced or stopped to adjust the beating of aheart to a second condition. The nerve may then be stimulated asubsequent time to readjust the beating of the heart to the firstcondition and the medical procedure then continued. The nerve may bestimulated, for example, using transvascular stimulation, endotrachaelstimulation, and/or endoesophageal stimulation. The first condition maybe a stopped or slowed condition. The second condition may be a beatingcondition. The heart may be stimulated to adjust the beating of theheart to the second condition. For example, the heart may be stimulatedwith a first cardiac electrode arrangement to adjust the beating of theheart to the second condition. Stimulation from the first cardiacelectrode arrangement may be evaluated to provide a first cardiacstimulation value. The heart may then be stimulated with a subsequentcardiac electrode arrangement and stimulation from this arrangement maythen be evaluated to provide a subsequent cardiac stimulation value. Adesired cardiac electrode arrangement may then be selected based on thefirst cardiac stimulation value and the subsequent cardiac stimulationvalue and the heart may be stimulated with the desired cardiac electrodearrangement. The first and subsequent cardiac electrode arrangements maybe one or more electrodes such as nerve stimulation electrodes, cardiacstimulation electrodes, clip electrodes, needle electrodes, probeelectrodes, pacing electrodes, patch electrodes, intravascularelectrodes, transcutaneous electrodes, intracutaneous electrodes,balloon-type electrodes, basket-type electrodes, umbrella-typeelectrodes, tape-type electrodes, suction-type electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes, electrodes, epicardialelectrodes, endotracheal electrodes and endoesophageal electrodes.

[0019] The method may also include delivering a drug such as abeta-blocker, a cholinergic agent, a cholinesterase inhibitor, a calciumchannel blocker, a sodium channel blocker, a potassium channel agent,adenosine, an adenosine receptor agonist, an adenosine deaminaseinhibitor, dipyridamole, a monoamine oxidase inhibitor, digoxin,digitalis, lignocaine, a bradykinin agent, a serotoninergic agonist, anantiarrythmic agent, a cardiac glycoside, a local anesthetic, atropine,a calcium solution, an agent that promotes heart rate, an agent thatpromotes heart contractions, dopamine, a catecholamine, an inotropeglucagon, a hormone, forskolin, epinephrine, norepinephrine, thyroidhormone, a phosphodiesterase inhibitor, prostacyclin, prostaglandin,methylxanthine, a P₂-purinoceptor agent, an ischemia agent, and a deltaopioid agonist may be delivered during the procedure. The drug may benaturally occurring or chemically synthesized.

[0020] The nerve may be a nerve such as a vagal nerve, a carotid sinusnerve, a fat pad.

[0021] The medical procedure may be surgical procedures, non-surgicalprocedures, endoscopic procedures, fluoroscopic procedures, stentdelivery procedures, aortic aneurysm repairs, cranial aneurysm repairs,delivery of drugs, delivery of biological agents, cardiac surgery withcardiopulmonary bypass circuits, cardiac surgery without cardiopulmonarybypass circuits, brain surgery, cardiograms, heart valve repair, heartvalve replacement, MAZE procedures, revascularization procedures,transmyocardial revascularization, percutaneous myocardialrevascularization, CABG procedures, anastomosis procedures, beatingheart surgery, vascular surgery, neurosurgery, brain surgery,electrophysiology procedures, diagnostic procedures, therapeuticprocedures, ablation procedures, ablation of arrhythmias, endovascularprocedures, treatment of the liver, treatment of the spleen, treatmentof the heart, treatment of the lungs, treatment of major blood vessels,non-invasive procedures, invasive procedures, port-access procedures,imaging procedures, CAT scan procedures, MRI procedures, gene therapyprocedures, cellular therapy procedures, cancer therapy procedures,radiation therapy procedures, transplantation procedures, coronaryangioplasty procedures, atherectomy procedures and atheroscleroticplaque removal procedures.

[0022] Another aspect of the present invention provides a device forperforming a medical procedure. The device includes a first electrodearrangement operatively arranged on a stimulation tube and a secondelectrode arrangement operatively arranged on a stimulation collar. Thefirst and the second electrode arrangements may comprise one or moreelectrodes such as nerve stimulation electrodes, endotrachealelectrodes, endoesophageal electrodes, intravascular electrodes,transcutaneous electrodes, intracutaneous electrodes, balloon-typeelectrodes, basket-type electrodes, umbrella-type electrodes, tape-typeelectrodes, suction-type electrodes, screw-type electrodes, barb-typeelectrodes, bipolar electrodes, monopolar electrodes, metal electrodes,wire electrodes, patch electrodes, cuff electrodes, clip electrodes,needle electrodes, probe electrodes, cardiac stimulation electrodes,pacing electrodes and epicardial electrodes. The device may also includea processor for evaluating stimulation from a set of electrodes, thepair of electrodes comprising at least one electrode from thestimulation tube and at least one electrode from the stimulation collar.

[0023] Another aspect of the present invention provides a system forperforming a medical procedure. The system includes a first electrodearrangement operatively arranged on a stimulation tube and a secondelectrode arrangement operatively arranged on a stimulation collar, aprocessor for evaluating stimulation from a set of electrodes, the pairof electrodes comprising at least one electrode from the stimulationtube and at least one electrode from the stimulation collar and acontroller for controlling stimulation from the set of electrodes. Thefirst and the second electrode arrangements may comprise one or moreelectrodes such as nerve stimulation electrodes, endotrachealelectrodes, endoesophageal electrodes, intravascular electrodes,transcutaneous electrodes, intracutaneous electrodes, balloon-typeelectrodes, basket-type electrodes, umbrella-type electrodes, tape-typeelectrodes, suction-type electrodes, screw-type electrodes, barb-typeelectrodes, bipolar electrodes, monopolar electrodes, metal electrodes,wire electrodes, patch electrodes, cuff electrodes, clip electrodes,needle electrodes, probe electrodes, cardiac stimulation electrodes,pacing electrodes and epicardial electrodes.

[0024] The system may also include drug delivery means such as a spray,a cream, an ointment, a medicament, a pill, a patch, a catheter, acannula, a needle and syringe, a pump, and an iontophoretic drugdelivery device for delivering drugs during the medical procedure.

[0025] Another aspect of the present invention provides a method ofperforming heart surgery. A nerve is stimulated with a first electrodearrangement to reduce the beating of a heart. Stimulation from the firstelectrode arrangement is evaluated to provide a first stimulation value.The nerve is then stimulated with a subsequent electrode arrangement andthe stimulation is evaluated to provide a subsequent stimulation value.A desired electrode arrangement is selected based on the firststimulation value and the subsequent stimulation value and the nerve isstimulated with the desired electrode arrangement. The heart is thenoperated upon. Stimulation of the nerve is then stopped and the heart isstimulated to cause beating of the heart. The nerve is thenre-stimulated to re-inhibit beating of the heart and the surgery iscontinued. The heart may also be stimulated with a first cardiacelectrode arrangement to adjust the beating of the heart to the secondcondition. Stimulation from the first cardiac electrode arrangement maybe evaluated to provide a first cardiac stimulation value. The heart maythen be stimulated with a subsequent cardiac electrode arrangement andstimulation from this arrangement may be evaluated to provide asubsequent cardiac stimulation value. A desired cardiac electrodearrangement may then be selected based on the first cardiac stimulationvalue and the subsequent cardiac stimulation value and the heart may bestimulated with the desired cardiac electrode arrangement.

[0026] The foregoing, and other, features and advantages of theinvention will become further apparent from the following detaileddescription of the presently preferred embodiments, read in conjunctionwith the accompanying drawings. The detailed description and drawingsare merely illustrative of the invention rather than limiting, the scopeof the invention being defined by the appended claims in equivalencethereof.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027]FIG. 1 is a schematic view of one embodiment of a stimulationsystem in accordance with the present invention;

[0028]FIG. 2 is a schematic view of one embodiment of an electrodedevice in accordance with the present invention;

[0029]FIG. 3 is a schematic view of one embodiment of an electrodedevice in accordance with the present invention;

[0030]FIG. 4 is a schematic view of one embodiment of an electrodedevice in accordance with the present invention;

[0031]FIG. 5 is a schematic view of one embodiment of an electrodedevice in accordance with the present invention;

[0032]FIG. 6 is a schematic view of one embodiment of an electrodedevice in accordance with the present invention;

[0033]FIG. 7 is a flow diagram of one embodiment of a method ofevaluating stimulation during a medical procedure in accordance with thepresent invention;

[0034]FIG. 8 is a flow diagram of one embodiment of a method ofperforming a medical procedure in accordance with the present invention;and

[0035]FIG. 9 is a timeline view of one embodiment of a system forcontrollably stopping or slowing the heart intermittently in a patientduring a medical procedure in accordance with the present invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

[0036]FIG. 1 shows a schematic view of one embodiment of a stimulationsystem for performing a medical procedure in accordance with the presentinvention at 200. Stimulation system 200 may include a nerve stimulator210, and a cardiac stimulator 220. System 200 may also feature acontroller 230 and a breathing regulator 240. System 200 may alsofeature pain relieving electrodes 260 and monitoring electrodes 270.

[0037] In one embodiment, nerve stimulator 210 may be used toelectrically manipulate cardiac rhythm by stimulating the vagus nerve.This vagal stimulation may produce asystole (slowing or stopping of theheart's beating.) Once this induced asystole is stopped, i.e. once thevagal stimulation is stopped, the heart may be allowed to return to itsusual cardiac rhythm. Alternatively, the heart may be paced with anelectrical pacing system, thereby maintaining a normal cardiac output.Vagal stimulation, alone or in combination with electrical pacing, maybe used selectively and intermittently to allow a surgeon to perform amedical procedure during intermittent periods of asystole.

[0038] It is known that stimulation of the vagus nerve can reduce thesinus rate, as well as prolong AV conduction time or, if stimulationenergies are high enough, induce AV node block. Use of vagal nervestimulation to treat supraventricular arrhythmias and angina pectoris isdisclosed in the article “Vagal Tuning” by Bilgutay et al., Journal ofThoracic and Cardiovascular Surgery, Vol. 56, No. 1, July, 1968, pp.71-82. It is also known that stimulation of the carotid sinus nerveproduces a similar result, as disclosed in the article “Carotid SinusNerve Stimulation in the Treatment of Angina Pectoris andSupraventricular Tachycardia” by Braunwald et al., published inCalifornia Medicine, Vol. 112, pp. 41-50, March, 1970.

[0039] As set forth in “Functional Anatomy of the Cardiac EfferentInnervation” by Randall et al., in Neurocardiology, edited by Kulbertuset al, Futura Publishing Co., 1988, direct surgical excision of the fatpad associated with the SA node affects the functioning of the SA nodewithout significantly affecting the AV node. Similarly, excision of thefat pad associated with the AV node affects functioning of the AV nodewithout significantly affecting the SA node.

[0040] As set forth in the article “Parasympathetic PostganglionicPathways to the Sinoatrial Node”, Bluemel et al., Am. J. Physiol. 259,(Heart Circ. Physiol. 28) H1504-H1510, 1990, stimulation of the fat padassociated with the SA node results in slowing of the sinus rate withoutthe accompanying prolongation of AV conduction time which normallyresults from vagal nerve stimulation. The article also indicates thatstimulation of the fat pad associated with the AV node is believed toproduce corresponding effects limited to the AV node, i.e., extension ofthe AV conduction time without concurrent slowing of the sinus rate.

[0041] As set forth in the article “Neural Effects on Sinus Rate andAtrial Ventricular Conduction Produced by Electrical Stimulation From aTransvenous Electrode Catheter in the Canine Right Pulmonary Artery” byCooper et al., published in Circulation Research, Vol. 46, No. 1,January, 1980, pp. 48-57, the fat pads associated with both the AV nodeand the SA node may be stimulated by means of electrodes located in theright pulmonary artery. The results obtained include both a depressionof the sinus rate and a prolongation of the AV conduction time inresponse to continuous stimulation at 2-80 Hz at up to 50 ma.

[0042] Generally in healthy individuals, the SA node functions as thepacemaker. Normal heart rhythm associated with the SA node is typicallyreferred to as sinus rhythm. When the SA node fails, the AV nodegenerally takes over creating a heart rate of approximately 35 to 60beats per minute. Heart rhythm associated with the AV node is typicallyreferred to as nodal rhythm. When the AV node itself is blocked orinjured, a new even slower pacemaker site may form at the junction ofthe AV node and the His bundle. Heart rhythm associated with thisjunction is typically referred to as junctional escape rhythm. When thisjunction site is inhibited, the Purkinje fibers in the His bundle orbelow may act as a pacemaker creating a heart rate of approximately 30beats per minute. Heart rhythm associated with the Purkinje fibers istypically referred to as idioventricular rhythm.

[0043] In one embodiment of the present invention, nerve stimulator 210may be used to electrically manipulate cardiac rhythm by stimulating thecarotid sinus nerve, the fat pad associated with the SA node, the fatpad associated with the AV node, the junction of the AV node and the Hisbundle and/or the Purkinje fibers.

[0044] In one embodiment of the present invention, nerve stimulator 210may be used alone or in combination with other heart rate inhibitingagents to temporarily stop or slow the beating heart, therebyeliminating or reducing heart motion and/or blood flow during a medicalprocedure. For example, the present invention may be used to eliminateor reduce motion in the anastomosis field during CABG procedures suchthat a facilitated anastomosis procedure may be performed safely andeffectively. The number of occasions that the vagal nerve may bestimulated depends on the type of medical procedure to be performed.Likewise, the type of medical procedure to be performed will dictate theduration of the individual electrical stimulations.

[0045] Nerve stimulator 210 may be powered by AC current, DC current orthe may be battery powered either by a disposable or re-chargeablebattery. Nerve stimulator 210 may be configured to synchronizeactivation and deactivation of breathing regulator 240 with vagalstimulation, thereby minimizing or eliminating unwanted heart and chestmotion associated with the patient's breathing. Nerve stimulator 210 maybe connected to a surgeon controlled switch box. A switch may beincorporated in or on one of the surgeon's instruments, such as surgicalsite retractor, or any other location easily and quickly accessed by thesurgeon for regulation of the nerve stimulator 210 by the surgeon. Theswitch may be, for example, a hand switch, a foot switch, or avoice-activated switch comprising voice-recognition technologies.

[0046] A visual and/or audible signal used to alert a surgeon to thecompletion or resumption of stimulation may be incorporated into nervestimulator 210. For example, a beeping tone or flashing light thatincreases in frequency as the stimulation period should end or begin maybe used.

[0047] Nerve stimulator 210 may be slaved to cardiac stimulator 220 orcardiac stimulator 220 may be slaved to nerve stimulator 210. Forexample, the output of cardiac stimulator 220 may be off whenever theoutput of nerve stimulator 210 is on. Software controlling cardiacstimulator 220 may be designed to automatically commence cardiac pacingif the heart does not resume beating within a pre-determined intervalafter cessation of vagal nerve stimulation. In addition, the softwarecontrolling nerve stimulator 210 may be designed to automatically stopvagal nerve stimulation if the heart has been stopped for too long.

[0048] The application of an electrical stimulus to the right or leftvagal nerve may include, but is not limited to bipolar and/or monopolartechniques. Nerve stimulation electrodes may be positioned within thebody of a patient, positioned on the skin of a patient and/or incombinations thereof. Electrical stimulation may be carried out on theright vagal nerve, the left vagal nerve or to both nerves simultaneouslyor sequentially. The present invention may include various electrodes,suitable for vagal nerve stimulation to temporarily stop or slow thebeating heart alone or in combination with other heart rate inhibitingagents.

[0049] Various techniques such as ultrasound, fluoroscopy andechocardiography may be used to facilitate positioning of electrodes. Inone embodiment of the present invention, the location of the vagal nervestimulation electrodes is chosen to elicit maximum bradycardiaeffectiveness while minimizing current spread to adjacent tissues andvessels and to prevent the induction of post stimulation tachycardia.Furthermore, a non-conductive material such as plastic may be employedto sufficiently enclose the electrodes of all the configurations toshield them from the surrounding tissues and vessels, while exposingtheir confronting edges and surfaces for positive contact with selectedtissues.

[0050] Nerve stimulation electrodes of nerve stimulator 210 may be, forexample, endotracheal electrodes or esophageal electrodes. Stimulationelectrodes may also be electrodes on a sheath or introducer. The sheathor introducer may or may not be splittable. The sheath or introducer maycomprise various materials including polymeric materials and metallicmaterials. The sheath or introducer may be used, for example, withtherapeutic or diagnostic catheters. For example, one type of catheterthe sheath or introducer may be used with is a venous catheter. Thesheath or introducer may comprise one or more electrodes. The electrodesmay be arranged, for example, on the surface of the sheath or introducerin a longitudinal pattern or in a circumferential pattern. Theseelectrodes may comprise an electrically conducting material, forexample, metal paint, metal tape, metal strips, metal buttons, metalfoil, metal wire and/or conductive plastic. The electrodes may be usedin a monopolar and/or bipolar arrangement. For example, two electrodeson the sheath or introducer may be used in a bipolar fashion or oneelectrode on the sheath or introducer may be used in a monopolar fashionin combination with an external skin electrode. The sheath comprisingone or more electrodes may be used with a variety of different medicalinstruments, e.g., catheters, probes, sensors, needles and the like, toprovide the stimulation, pacing, pain control and/or sensingcapabilities to the instrument.

[0051] Nerve stimulation electrodes may also be electrodes on a cannula.The cannula may comprise various materials including polymeric materialsand metallic materials. In addition, to stimulation, the cannula may beused, for example, for therapeutic or diagnostic purposes. The cannulamay comprise one or more balloons. One or more electrodes may bearranged, for example, on the surface of the cannula in a longitudinalpattern or in a circumferential pattern. The electrodes may also bearranged on one or more balloons attached to the cannula. The electrodesmay comprise an electrically conducting material, for example, metalpaint, metal tape, metal strips, metal buttons, metal foil, metal wireand/or conductive plastic. The electrodes may be used in a monopolarand/or bipolar arrangement. For example, two electrodes on the cannulamay be used in a bipolar fashion or one electrode on the cannula may beused in a monopolar fashion in combination with an external skinelectrode.

[0052]FIG. 2 shows one embodiment of an electrode device comprisingendotracheal electrodes in accordance with the present invention at 10A.Electrode device 10A may comprise a tube 100 suitable for insertionthrough a patient's nose or mouth and into the patient's trachea.

[0053] Electrode device 10A may include a first electrode arrangementattached to tube 100. This electrode arrangement may be used toaccomplish stimulation on such body components as nerves, muscles, theheart, and the lungs. This stimulation may be used to controllably stopor start an organ such as the heart or lungs or to ease pain. Theelectrode arrangement may also be used to sense or monitor physiologicalfunctions.

[0054] Tube 100 may comprise a flexible, non-electrically conductingtube having a proximal end 11 and a distal end 12. Tube 100 may be madeof a material selected for its stiffness and flexibility to allow tube100 to conform readily to the shape of the patient's trachea withminimal trauma to tissue. For example, silicone rubber, polyurethane orother polymers or materials may be used. The outer diameter and lengthof tube 100 may vary depending upon size of the patient for whom it isintended. Lubricating gels or creams may be used during placement of thedevice. These lubricating gels or creams may or may not be conductive.Tube 100 may include a biocompatible coating, for example, a slipcoating for easier insertion.

[0055] Tube 100 may also include main lumen 20 for transporting gases toand from the lungs. Main lumen 20 runs from the proximal end of tube 100to the distal end of tube 100. Tube 100 may be connected at proximal end11 to a breathing regulator, which injects and withdraws air from thelungs. Proximal end 11 may include a standard tracheal tube adapter foranesthesia gas connection. Proximal end 11 may include a stop whichengages the face of the patient so as to prevent further insertion whenthe distal end is in the proper location.

[0056] An inflatable cuff 13 may be located near distal end 12 of tube100. Inflatable cuffs are typically used on tracheal tubes to preventair from escaping by passing between the tube and the trachea wall.Inflatable cuffs may also be used to stabilize the location ofelectrodes in the trachea. Inflatable cuff 13 is shown in an deflatedcondition in FIG. 2 and can be inflated by use of a cuff-inflatingconduit 15, which may be attached to a source of compressed gas (e.g.,air) or fluid (e.g., saline). Cuff-inflating conduit 15 may be a lumenwhich communicates with the interior of the cuff through a port in thetube. Inflatable cuff 13 may be made of a very soft rubber-like materialwell known in the catheter art. A check valve may be used to controlinflation and deflation of the cuff. Tube 100 may or may not include oneor more cuffs. A single inflation lumen in communication with multiplecuffs may be used to inflate the cuffs or each cuff may have its owninflation lumen. Tube 100 may include positioning marks or otherpositioning technologies.

[0057] Associated with tube 100 is an arrangement of electrodes 16.These electrodes may comprise an electrically conducting material, forexample, metal paint, metal tape, metal strips, metal buttons, metalfoil, metal wire and/or conductive plastic. The electrodes may be ringelectrodes, wire electrodes, button electrodes and/or foil electrodes.The electrodes may be used in a monopolar and/or bipolar arrangement.For example, two electrodes on tube 100 may be used in a bipolar fashionor one electrode on tube 100 may be used in a monopolar fashion incombination with an external skin electrode. The electrodes may bearranged parallel to the axis of tube 100 and/or the electrodes may bearranged circumferentially to the axis of tube 100. Tube 100 maycomprise one or more electrodes. The electrodes may be located proximalto an inflatable cuff, distal to an inflatable cuff, on one or moreinflatable cuffs and/or combinations thereof. For example, in FIG. 2,electrode arrangement 16 comprises an array of electrodes located on theouter surface of inflatable cuff 13. Placement of electrodes on aninflatable cuff may help the electrodes make improved contact with theinner surface of the trachea when the cuff is inflated.

[0058]FIG. 3 shows one embodiment of an electrode device comprisingendotracheal electrodes in accordance with the present invention at 10B.Electrode device 10B may comprise tube 100, for example, as describedabove, and a collar 101. Collar 101 may be suitable for externalplacement on a portion of the body such as, for example, around theneck. Electrode device 10B may include a first electrode arrangementattached to tube 100 and a second electrode arrangement attached tocollar 101. These electrode arrangements may be used to accomplishstimulation on such body components as nerves, muscles, the heart, andthe lungs. This stimulation may be used to controllably stop or start anorgan such as the heart or lungs or to ease pain. The electrodes mayalso be used to sense or monitor physiological functions.

[0059] Collar 101 may comprise a flexible, non-electrically conductingmaterial selected for its stiffness and flexibility to allow collar 101to conform readily to the shape of the patient's neck. The collar may beadjustable to allow it to fit appropriately the neck size of the patientfor whom it is intended. Associated with collar 101 is an arrangement ofelectrodes 116. These electrodes may comprise an electrically conductingmaterial, for example, metal paint, metal tape, metal strips, metalbuttons, metal foil, metal wire and/or conductive plastic. Theelectrodes may be wire electrodes, button electrodes and/or foilelectrodes. The electrodes may be arranged circumferentially around theneck of a patient. Collar 101 may comprise one or more electrodes.Conductive gels or creams may be used in combination with the collar tohelp improve electrical contact of electrodes 116 with the body of thepatient.

[0060]FIG. 4 shows one embodiment of an electrode device comprisingendotracheal electrodes in accordance with the present invention at 10C.Electrode device 10C may comprise tube 100, for example, as describedabove, and one or more external electrodes 102. Electrodes 102 may besuitable for external placement on a portion of the body such as, forexample, on the neck or chest. Electrode device 10C may include a firstelectrode arrangement attached to tube 100 and a second electrodearrangement external to the patient's body, for example externalelectrode 102. Electrode arrangement 102 may comprise one or moretypical external electrodes, for example skin or patch electrodes. Thefirst and second electrode arrangements may be used to accomplishstimulation on such body components as nerves, muscles, the heart, andthe lungs. This stimulation may be used to controllably stop or start anorgan such as the heart or lungs or to ease pain. The electrodes mayalso be used to sense or monitor physiological functions.

[0061] In FIG. 4, tube 100 is shown comprising an arrangement of metalwire electrodes 16 located on the outer surface of inflatable cuff 13.In this particular embodiment, electrodes 16 are shown as wires that runfrom a location between the two tube ends 11 and 12 toward distal end 12in a direction parallel to the tube's central axis. Each electrode wiremay have a first portion, located between proximal end 11 and distal end12, and insulated against electrical contact. Each electrode may alsohave a second wire portion located on outer surface of cuff 13. Eachsecond wire portion located on outer surface of cuff 13 is uninsulatedand capable of forming an electrical contact. This contact may be formedwith a body component, such as, for example adjacent muscles or nerves.

[0062] Tube 100 comprising at least two electrodes may be used in abipolar fashion without the use of one or more external electrodes. Forexample, tube 100 may be used without the use of collar 101 or externalelectrode 102. Tube 100 comprising one or more electrodes may be used ina monopolar fashion with the use of one or more external electrodes, forexample collar 101 or external electrode 102. In addition, electrodes ofdevices 10A, 10B and 10C, for example, may comprise any means capable offorming electrical contact with, for example, nerve stimulator 210, suchas connecting plugs, alligator clips or insulated wires with bared ends.

[0063]FIG. 5 shows one embodiment of an electrode device comprisingesophageal electrodes in accordance with the present invention at 10D.Electrode device 10D may comprise a tube 103 suitable for insertionthrough a patient's nose or mouth and into the patient's esophagus.Electrode device 10D may comprise one or more external electrodes 102.Electrodes 102 may be suitable for external placement on a portion ofthe body such as, for example, on the neck or chest. Electrode device10D may include a first electrode arrangement attached to tube 103 and asecond electrode arrangement external to the patient's body, for exampleexternal electrode 102. Electrode arrangement 102 may comprise one ormore typical external electrodes, for example skin or patch electrodes.The first and second electrode arrangements may be used to accomplishstimulation on such body components as nerves, muscles, the heart, andthe lungs. This stimulation may be used to controllably stop or start anorgan such as the heart or lungs or to ease pain. The electrodes mayalso be used to sense or monitor physiological functions.

[0064] Tube 103 may comprise a flexible, non-electrically conductingtube having a proximal end 31 and a distal end 32. Tube 103 may be madeof a material selected for its stiffness and flexibility to allow tube103 to conform readily to the shape of the patient's esophagus withminimal trauma to tissue. For example, silicone rubber, polyurethane orother polymers or materials may be used. The outer diameter and lengthof tube 103 may vary depending upon size of the patient for whom it isintended. Lubricating gels or creams may be used during placement of thedevice. These lubricating gels or creams may or may not be conductive.Tube 103 may include a biocompatible coating, for example, a slipcoating for easier insertion. Tube 103 may include positioning marks orother positioning technologies.

[0065] Associated with tube 103 is an arrangement of electrodes 16.These electrodes may comprise an electrically conducting material, forexample, metal paint, metal tape, metal strips, metal buttons, metalfoil, metal wire and/or conductive plastic. The electrodes may be ringelectrodes, wire electrodes, button electrodes and/or foil electrodes.The electrodes may be used in a monopolar and/or bipolar arrangement.For example, two electrodes on tube 103 may be used in a bipolar fashionor one electrode on tube 103 may be used in a monopolar fashion incombination with an external skin electrode 102. The electrodes may bearranged parallel to the axis of tube 103 and/or the electrodes may bearranged circumferentially to the axis of tube 103. Tube 103 maycomprise one or more electrodes. The electrodes may be located proximalto an inflatable cuff or hole, distal to an inflatable cuff or hole, onone or more inflatable cuffs and/or combinations thereof. For example,in FIG. 5, electrode arrangement 16 comprises an array of wireelectrodes wrapped around the outer surface of tube 103 and arrangedaround multiple holes 14.

[0066] One or more holes 14 in tube 103 in the area of the electrodes 16provides a means of ensuring better electrical contact with theesophageal wall and electrodes 16 when suction is introduced throughsuction conduit 18. Suction conduit 18 may be attached to a vacuumsource. Suction conduit 18 may be a lumen which communicates with one ormore holes 14 through a port in tube 103. A variety of securing meansbesides holes 14 may be used for improving electrical contact betweenelectrodes and esophageal wall, for example suction pods or a stickybiocompatible substance may be used.

[0067]FIG. 6 shows one embodiment of an electrode device comprisingesophageal electrodes in accordance with the present invention at 10E.Electrode device 10E may comprise a tube 103 suitable for insertionthrough a patient's nose or mouth and into the patient's esophagus.Electrode device 10D may comprise one or more external electrodes 102 asdescribed above.

[0068] As shown in FIG. 6, an inflatable cuff 13 may be located neardistal end 32 of tube 103. Inflatable cuff 13 may be used to stabilizethe location of electrodes in the esophagus. Inflatable cuff 13 is shownin an inflated condition in FIG. 5 and can be inflated and deflated byuse of a cuff-inflating conduit 15, which may be attached to a source ofcompressed gas (e.g., air) or fluid (e.g., saline). Cuff-inflatingconduit 15 may be a lumen which communicates with the interior of thecuff through a port in the tube. Inflatable cuff 13 may be made of avery soft rubber-like material well known in the catheter art. A checkvalve may be used to control inflation and deflation of the cuff. Tube103 may or may not include one or more cuffs. A single inflation lumenin communication with multiple cuffs may be used to inflate the cuffs oreach cuff may have its own inflation lumen. Placement of electrodes 16on inflatable cuff 13 may help the electrodes make improved contact withthe inner surface of the esophagus when the cuff is inflated. Tube 103may include positioning marks or other positioning technologies.

[0069] Tube 103 comprising at least two electrodes may be used in abipolar fashion without the use of one or more external electrodes. Forexample, tube 103 may be used without the use of external electrode 102.Tube 103 comprising one or more electrodes may be used in a monopolarfashion with the use of one or more external electrodes, for exampleexternal electrode 102. In addition, electrodes of devices 10D and 10E,for example, may comprise any means capable of forming electricalcontact with, for example, nerve stimulator 210, such as connectingplugs, alligator clips or insulated wires with bared ends.

[0070] System 200 may also include cardiac stimulator 220 which may beused to stimulate the heart as desired. As with nerve stimulator 210,cardiac stimulator 220 may be intermittently stopped and started toallow the surgeon to perform individual steps of a medical procedure.

[0071] Cardiac stimulator 220 may further comprise a conventionalventricular demand pacer or dual chamber (atrial-ventricular) pacer.Cardiac stimulator 220 may be powered by AC current, DC current or maybe battery powered either by a disposable or re-chargeable battery.Cardiac stimulator 220 may be configured to synchronize activation anddeactivation of breathing regulator 240 with pacing, thereby minimizingor eliminating unwanted heart and chest motion associated with thepatient's breathing. Cardiac stimulator 220 may also comprise anyconventional pacing device suitable for ventricular demand pacing.

[0072] Cardiac stimulator 220 may be combined in a single unit with aswitch box. Cardiac stimulator 220 may comprise a surgeon controlledswitch box. A switch may be incorporated in or on one of the surgeon'sinstruments, such as surgical site retractor, or any other locationeasily and quickly accessed by the surgeon for regulation of the cardiacstimulator by the surgeon. The switch may be, for example, a handswitch, a foot switch, or a voice-activated switch comprisingvoice-recognition technologies. A single switch may be used to regulateboth cardiac stimulator 220 and nerve stimulator 210.

[0073] A visual and/or audible signal used to prepare a surgeon for theresumption of pacing may be incorporated into cardiac stimulator 220.For example, a beeping tone or flashing light that increases infrequency as the pacing period ends may be used. A single signalingmethod or device may be used for both cardiac stimulator 220 and nervestimulator 210.

[0074] Cardiac stimulator 220 may comprise any type of electrodessuitable for stimulating the heart, for example, non-invasiveelectrodes, e.g., clips, or invasive electrodes, e.g., needles or probesmay be used. Cardiac stimulation electrodes may be positioned through athoracotomy, sternotomy, endoscopically through a percutaneous port,through a stab wound or puncture, through a small incision in the chest,placed on the chest or in combinations thereof. The present inventionmay also use various electrodes, catheters and electrode catheterssuitable for pacing the heart, e.g., epicardial, endocardial,patch-type, intravascular, balloon-type, basket-type, umbrella-type,tape-type electrodes, suction-type, pacing electrodes, endotrachealelectrodes, esophageal electrodes, transcutaneous electrodes,intracutaneous electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, catheter sheath electrodes, introducer electrodes, cannulaelectrodes and cuff electrodes. The electrodes may comprise anelectrically conducting material, for example, metal paint, metal tape,metal strips, metal buttons, metal foil, metal wire and/or conductiveplastic. Guided or steerable catheter devices comprising electrodes maybe used alone or in combination with the electrodes.

[0075] Cardiac stimulator 220 may be capable of producing specificpacing and stimulation regimes. For example, cardiac stimulator 220 maybe capable of sensing and treating electromechanical dissociation (EMD)of the heart as disclosed in U.S. Pat. No. 6,253,108 to inventorsRosborough and Deno and/or cardiac stimulator 220 may be capable ofsensing and treating tachyarrhythmia of the heart using specific pacingand/or stimulation regimes. In some patients, EMD and/or tachyarrhythmiamay occur during and/or post the medical procedure. The pacing andstimulation regimes may be specific for periods before the procedure,during the procedure and post the procedure. The pacing and stimulationregimes may also be specific for patient recovery, if the patients donot respond following a period of cardiac asystole.

[0076] Nerve stimulator 210 and/or cardiac stimulator 220 may be slavedto a robotic system or a robotic system may be slaved to nervestimulator 210 and/or cardiac stimulator 220. Breathing regulator 240and other components may also be slaved to such a system. Computer- andvoice-controlled robotic systems that position and maneuver endoscopesand/or other surgical instruments for performing microsurgicalprocedures such as anastomoses through small incisions may be used by asurgeon to perform precise and delicate maneuvers. These robotic systemsmay allow a surgeon to perform a variety of microsurgical proceduresincluding endoscopic CABG. Endoscopic CABG may allow multiple occludedcoronary arteries to be bypassed without a thoracotomy ormini-thoracotomy. Heart valve repair and replacement may also be othersurgical applications for these robotic systems. In general, roboticsystems may include head-mounted displays which integrate 3-Dvisualization of surgical anatomy and related diagnostic and monitoringdata, miniature high resolution 2-D and 3-D digital cameras, a computer,a high power light source and a standard video monitor.

[0077] System 200 may also include a breathing regulator 240. In oneembodiment, the breathing regulator 240 may be used to stimulate thephrenic nerve in order to provide a diaphragmatic pacemaker. Breathingregulator 240 may comprise one or more electrodes for supplyingelectrical current to the phrenic nerve to control breathing duringvagal and/or cardiac stimulation and/or destimulation. Electrodes usedto stimulate the phrenic nerve may be, for example, non-invasive, e.g.,clips, or invasive, e.g., needles or probes. The application of anelectrical stimulus to the phrenic nerve may include, but is not limitedto bipolar and/or monopolar techniques. Different electrode positionsare accessible through various access openings, for example, in thecervical or thorax regions. Nerve stimulation electrodes may bepositioned through a thoracotomy, sternotomy, endoscopically through apercutaneous port, through a stab wound or puncture, through a smallincision, placed on the skin or in combinations thereof. The presentinvention may include various electrodes, catheters and electrodecatheters suitable for phrenic nerve stimulation to control breathing.

[0078] Phrenic nerve stimulation electrodes may be intravascular,patch-type, balloon-type, basket-type, umbrella-type, tape-type,cuff-type, suction-type, screw-type, barb-type, bipolar, monopolar,metal, wire, endotracheal electrodes, esophageal electrodes,intravascular electrodes, transcutaneous electrodes, catheter sheathelectrodes, introducer electrodes, cannula electrodes or intracutaneouselectrodes. The electrodes may comprise an electrically conductingmaterial, for example, metal paint, metal tape, metal strips, metalbuttons, metal foil, metal wire and/or conductive plastic. Guided orsteerable catheter devices comprising electrodes may be used alone or incombination with the nerve stimulation electrodes. For example, acatheter comprising one or more wire, metal strips or metal foilelectrodes or electrode arrays may be used. The catheter may comprise,for example, a balloon that may be inflated with air or liquid to pressthe electrodes firmly against a vessel wall that lays adjacent thephrenic nerve.

[0079] Phrenic nerve stimulation electrodes may be oriented in anyfashion along a device, including longitudinally or transversely.Various techniques such as ultrasound, fluoroscopy and echocardiographymay be used to facilitate positioning of the electrodes. If desired ornecessary, avoidance of obstruction of blood flow may be achieved withnotched catheter designs or with catheters that incorporate one or moretunnels or passageways.

[0080] In another embodiment, the breathing regulator may comprise aconnector that interfaces with a patient's respirator, and sends a logicsignal to activate or deactivate the respirator to control breathingduring vagal and/or cardiac stimulation and/or destimulation.

[0081] System 200 may also include electrodes for relieving pain such asindicated at 260. In one embodiment, pain-relieving electrodes may beused to stimulate the spinal cord. Pain relieving electrodes 260 maycomprise one or more electrodes for supplying electrical current tocontrol pain during vagal and/or cardiac stimulation and/ordestimulation. Electrodes used to relieve pain may be, for example,non-invasive, e.g., clips, or invasive, e.g., needles or probes. Theapplication of an electrical stimulus to relieve pain may include, butis not limited to bipolar and/or monopolar techniques. The electrodesmay comprise an electrically conducting material, for example, metalpaint, metal tape, metal strips, metal buttons, metal foil, metal wireand/or conductive plastic. Different electrode positions are accessiblethrough various access openings, for example, in the cervical or thoraxregions. Nerve stimulation electrodes may be positioned through athoracotomy, sternotomy, endoscopically through a percutaneous port,through a stab wound or puncture, through a small incision, placed onthe skin or in combinations thereof. The present invention may includevarious electrodes, catheters and electrode catheters suitable for thecontrol of pain.

[0082] Pain relieving electrodes 260 may be intravascular, patch-type,balloon-type, basket-type, umbrella-type, tape-type, cuff-type,suction-type, screw-type, barb-type, bipolar, monopolar, metal, wire,endotracheal, endoesophageal, intravascular, transcutaneous orintracutaneous electrodes. Guided or steerable catheter devicescomprising electrodes may be used alone or in combination with the nervestimulation electrodes. For example, a catheter comprising one or morewire, metal strips or metal foil electrodes or electrode arrays may beused. The catheter may comprise, for example, a balloon that may beinflated with air or liquid to press the electrodes firmly against avessel wall that lays adjacent the nerve or portion of the spine to bestimulated.

[0083] Pain relieving electrodes may be oriented in any fashion alongthe device, including longitudinally or transversely. Various techniquessuch as ultrasound, fluoroscopy and echocardiography may be used tofacilitate positioning of the electrodes. If desired or necessary,avoidance of obstruction of blood flow may be achieved with notchedcatheter designs or with catheters that incorporate one or more tunnelsor passageways.

[0084] System 200 may also include sensing electrodes 270 to monitor oneor more sites of stimulation. Sensing electrodes may be the sameelectrodes used for nerve stimulation, cardiac stimulation or painrelieving and/or they may be positioned adjacent one or more of thesites of stimulation described above.

[0085] System 200 may also include controller 230. Controller 230 may beused to gather information from nerve stimulator 210 and cardiacstimulator 220. Controller 230 may also be used to control thestimulation levels and stimulation duration of nerve stimulator 210 andcardiac stimulator 220. Controller 230 may also gather and processinformation from the various components of system 200, in particularsensing electrodes 270. This information may be used to adjuststimulation levels and stimulation times of nerve stimulator 210,cardiac stimulator 220, breathing regulator 240 and/or pain relievingelectrodes 260. This adjustment may be based, for example, on datareceived from monitoring electrodes 270.

[0086] System 200 may incorporate one or more switches to facilitateregulation of the various components by the surgeon. One such switch isindicated schematically at 250. The switch may be, for example, a handswitch, a foot switch or a voice-activated switch comprisingvoice-recognition technologies. The switch may be incorporated on one ofthe surgeon's instruments, such as surgical site retractor, or any otherlocation easily and quickly accessed by the surgeon.

[0087] System 200 may also incorporate means for indicating the statusof various components to the surgeon such as feedback means 280. Thesefeedback means may comprise a display, a numerical display, gauges, amonitor display or audio feedback. Feedback means 280 may also compriseone or more visual and/or audible signals used to prepare a surgeon forthe start or stop of nerve stimulation and/or cardiac stimulation.Alternatively, the feedback means may be incorporated on one of thesurgeon's instruments, such as surgical site retractor, or any otherlocation easily and quickly accessed by the surgeon.

[0088]FIG. 7 shows a flow diagram of one embodiment of the presentinvention at 300. Stimulation from at least one electrode of a firstelectrode arrangement may begin at block 310. In one embodiment of theinvention, the first electrode arrangement may be located on tube 100 ofdevice 10. At block 320, stimulation from at least one electrode of asecond electrode arrangement is begun. In one embodiment of theinvention, the second electrode arrangement may be located on collar 101of device 10. At block 330, data is gathered regarding the stimulation.For example, data may be gathered from sensing electrodes 270.Alternatively, one or more of the electrodes delivering stimulation mayalso deliver data to be gathered (i.e. may act as both stimulation andsensing electrodes.) At block 340, the stimulation is evaluated based onthe data gathered at block 330. In one embodiment of the invention, thestimulation may be compared to a previously decided value ofstimulation. If the stimulation is satisfactory, the stimulation may becontinued using the first and second electrode arrangement from blocks310, 320 (block 350). Alternatively, if the stimulation is notsatisfactory, the process may be repeated as designated by loop 365 andanother first electrode arrangement is chosen (block 310) followed byanother second electrode arrangement (block 320) and further evaluation(blocks 330, 340). This process may repeated until the most satisfactorystimulation is received.

[0089]FIG. 8 shows a flow diagram of one embodiment of the presentinvention. The patient is prepared for a medical procedure at 500.

[0090] At block 510, a nerve that controls the beating of the heart isstimulated. Such a nerve may be for example a vagal nerve. In oneembodiment of the invention, at block 510, the routine described in FIG.3 occurs until the electrode pairing resulting in the most satisfactorystimulation is achieved.

[0091] During the procedure 500, one or more of a variety ofpharmacological agents or drugs may be delivered (Block 515). Thesedrugs may produce reversible asystole of a heart while maintaining theability of the heart to be electrically paced. Other drugs may beadministered for a variety of functions and purposes as described below.As seen in FIG. 4, drugs delivered at Block 515 may be administered atthe beginning of the procedure, intermittently during the procedure,continuously during the procedure, or following the procedure.

[0092] Drugs, drug formulations or compositions suitable foradministration to a patient during a medical procedure may include apharmaceutically acceptable carrier or solution in an appropriatedosage. There are a number of pharmaceutically acceptable carriers thatmay be used for delivery of various drugs, for example, via directinjection, intravenous delivery, intramuscular delivery, oral delivery,topical delivery, hypodermal delivery, suppository delivery, transdermaldelivery, epicardial delivery, intraparenteral delivery and/orinhalation delivery. Pharmaceutically acceptable carriers include anumber of solutions, preferably sterile, for example, water, saline,Ringer's solution and/or sugar solutions such as dextrose in water orsaline. Other possible carriers that may be used include a oil, sodiumcitrate, citric acid, amino acids, lactate, mannitol, maltose, glycerol,sucrose, ammonium chloride, sodium chloride, potassium chloride, calciumchloride, sodium lactate, and/or sodium bicarbonate. Carrier solutionsmay or may not be buffered.

[0093] Drug formulations or compositions may include antioxidants orpreservatives such as ascorbic acid. Other preservatives includebenzalkonium chloride, methyl-paraben, propyl-paraben, and chlorbutanol.They may also be in a pharmaceutically acceptable form for parenteraladministration, for example to the cardiovascular system, or directly tothe heart, such as intracoronary infusion or injection. Drugformulations or compositions may comprise agents that provide asynergistic effect when administered together. A synergistic effectbetween two or more drugs or agents may reduce the amount that normallyis required for therapeutic delivery of an individual drug or agent. Twoor more drugs may be administered, for example, sequentially orsimultaneously. Drugs may be administered via one or more bolusinjections and/or infusions or combinations thereof. The injectionsand/or infusions may be continuous or intermittent. Drugs may beadministered, for example, systemically or locally, for example, to theheart, to a coronary artery and/or vein, to a pulmonary artery and/orvein, to the right atrium and/or ventricle, to the left atrium and/orventricle, to the aorta, to the AV node, to the SA node, to a nerveand/or to the coronary sinus. Drugs may be administered or delivered viaintravenous, intracoronary and/or intraventricular administration in asuitable carrier. Examples of arteries that may be used to deliver drugsto the AV node include the AV node artery, the right coronary artery,the right descending coronary artery, the left coronary artery, the leftanterior descending coronary artery and Kugel's artery. Drugs may bedelivered systemically, for example, via oral, transdermal, intranasal,suppository or inhalation methods. Drugs also may be delivered via apill, a spray, a cream, an ointment or a medicament formulation.

[0094] Drugs may be delivered via a drug delivery device that maycomprise a catheter, such as a drug delivery catheter or a guidecatheter, a patch, such as a transepicardial patch that slowly releasesdrugs directly into the myocardium, a cannula, a pump and/or ahypodermic needle and syringe assembly. A drug delivery catheter mayinclude an expandable member, e.g., a low-pressure balloon, and a shafthaving a distal portion, wherein the expandable member is disposed alongthe distal portion. A catheter for drug delivery may comprise one ormore lumens and may be delivered endovascularly via insertion into ablood vessel, e.g., an artery such as a femoral, radial, subcdavian orcoronary artery. The catheter can be guided into a desired positionusing various guidance techniques, e.g., flouroscopic guidance and/or aguiding catheter or guide wire techniques.

[0095] Drugs may be delivered via an iontophoretic drug delivery deviceplaced on the heart. In general, the delivery of ionized drugs may beenhanced via a small current applied across two electrodes. Positiveions may be introduced into the tissues from the positive pole, ornegative ions from the negative pole. The use of iontophoresis maymarkedly facilitate the transport of certain ionized drug molecules. Forexample, lidocaine hydrochloride may be applied to the heart via a drugpatch comprising the drug. A positive electrode could be placed over thepatch and current passed. The negative electrode would contact the heartor other body part at some desired distance point to complete thecircuit. One or more of the electrodes may also be used as nervestimulation electrodes 210 or as cardiac stimulation electrodes 220.

[0096] The two divisions of the autonomic nervous system that regulatethe heart have opposite functions. First, the adrenergic or sympatheticnervous system increases heart rate by releasing epinephrine andnorepinephrine. Second, the parasympathetic system also known as thecholinergic nervous system or the vagal nervous system decreases heartrate by releasing acetylcholine. Catecholamines such as norepinephrine(also called noradrenaline) and epinephrine (also called adrenaline) areagonists for beta-adrenergic receptors. An agonist is a stimulantbiomolecule or agent that binds to a receptor.

[0097] Beta-adrenergic receptor blocking agents compete withbeta-adrenergic receptor stimulating agents for available beta-receptorsites. When access to beta-receptor sites are blocked by receptorblocking agents, also known as beta-adrenergic blockade, thechronotropic or heart rate, inotropic or contractility, and vasodilatorresponses to receptor stimulating agents are decreased proportionately.Therefore, beta-adrenergic receptor blocking agents are agents that arecapable of blocking beta-adrenergic receptor sites.

[0098] Since beta-adrenergic receptors are concerned with contractilityand heart rate, stimulation of beta-adrenergic receptors, in general,increases heart rate, the contractility of the heart and the rate ofconduction of electrical impulses through the AV node and the conductionsystem.

[0099] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) beta-adrenergic receptorblocking agents. Beta-adrenergic receptor blocking agents orP-adrenergic blocking agents are also known as beta-blockers orP-blockers and as class II antiarrhythmics.

[0100] The term “beta-blocker” appearing herein may refer to one or moreagents that antagonize the effects of beta-stimulating catecholamines byblocking the catecholamines from binding to the beta-receptors. Examplesof beta-blockers include, but are not limited to, acebutolol,alprenolol, atenolol, betantolol, betaxolol, bevantolol, bisoprolol,carterolol, celiprolol, chlorthalidone, esmolol, labetalol, metoprolol,nadolol, penbutolol, pindolol, propranolol, oxprenolol, sotalol,teratolol, timolol and combinations, mixtures and/or salts thereof.

[0101] The effects of administered beta-blockers may be reversed byadministration of beta-receptor agonists, e.g., dobutamine orisoproterenol.

[0102] The parasympathetic or cholinergic system participates in controlof heart rate via the sinoatrial (SA) node, where it reduces heart rate.Other cholinergic effects include inhibition of the AV node and aninhibitory effect on contractile force. The cholinergic system actsthrough the vagal nerve to release acetylcholine, which, in turn,stimulates cholinergic receptors. Cholinergic receptors are also knownas muscarinic receptors. Stimulation of the cholinergic receptorsdecreases the formation of cAMP. Stimulation of cholinergic receptorsgenerally has an opposite effect on heart rate compared to stimulationof beta-adrenergic receptors. For example, beta-adrenergic stimulationincreases heart rate, whereas cholinergic stimulation decreases it. Whenvagal tone is high and adrenergic tone is low, there is a marked slowingof the heart (sinus bradycardia). Acetylcholine effectively reduces theamplitude, rate of increase and duration of the SA node actionpotential. During vagal nerve stimulation, the SA node does not arrest.Rather, pacemaker function may shift to cells that fire at a slowerrate. In addition, acetylcholine may help open certain potassiumchannels thereby creating an outward flow of potassium ions andhyperpolarization. Acetylcholine also slows conduction through the AVnode.

[0103] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) cholinergic agent. The term“cholinergic agent” appearing herein may refer to one or morecholinergic receptor modulators or agonists. Examples of cholinergicagents include, but are not limited to, acetylcholine, carbachol(carbamyl choline chloride), bethanechol, methacholine, arecoline,norarecoline and combinations, mixtures and/or salts thereof.

[0104] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized cholinesterase inhibitor. The term“cholinesterase inhibitor” appearing herein may refer to one or moreagents that prolong the action of acetylcholine by inhibiting itsdestruction or hydrolysis by cholinesterase. Cholinesterase inhibitorsare also known as acetylcholinesterase inhibitors. Examples ofcholinesterase inhibitors include, but are not limited to, edrophonium,neostigmine, neostigmine methylsulfate, pyridostigmine, tacrine andcombinations, mixtures and/or salts thereof.

[0105] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) P₂-purinoceptor agents. Theterm “P₂-purinoceptor agent” appearing herein may refer to one or moreP₂-purinoceptor modulators, mediators, agonists and/or antagonistsdisclosed in U.S. Pat. No. 5,874,420 to inventor Pelleg.P₂-purinoceptors are specific cell surface receptors found on vagalnerve terminals. Vagal tone may be modulated (increased or decreased) bythe administration of one or more P₂-purinoceptor agents which activateor block these P₂-purinoceptor receptors. Examples of P₂-purinoceptoragents include, but are not limited to, P₂-purinoceptor agonists,P₂-purinoceptor antagonists, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), Reactive Blue 2, Cibacron Blue, adenosine5′-triphosphate (ATP), ATP analogues, capsaicin and combinations,mixtures and/or salts thereof.

[0106] There are ion-selective channels within certain cell membranes.These ion selective channels include calcium channels, sodium channelsand/or potassium channels. Therefore, other drugs, drug formulationsand/or drug compositions that may be used according to this inventionmay include any naturally occurring or chemically synthesized calciumchannel blocker. Calcium channel blockers inhibit the inward flux ofcalcium ions across cell membranes of arterial smooth muscle cells andmyocardial cells. Therefore, the term “calcium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of calcium ions across a cell membrane. The calcium channel isgenerally concerned with the triggering of the contractile cycle.Calcium channel blockers are also known as calcium ion influxinhibitors, slow channel blockers, calcium ion antagonists, calciumchannel antagonist drugs and as class IV antiarrhythmics. A commonlyused calcium channel blocker is verapamil.

[0107] Administration of a calcium channel blocker, e.g., verapamil,generally prolongs the effective refractory period within the AV nodeand slows AV conduction in a rate-related manner, since the electricalactivity through the AV node depends significantly upon the influx ofcalcium ions through the slow channel. A calcium channel blocker has theability to slow a patient's heart rate, as well as produce AV block.Examples of calcium channel blockers include, but are not limited to,amiloride, amlodipine, bepridil, diltiazem, felodipine, isradipine,mibefradil, nicardipine, nifedipine (dihydropyridines), nickel,nimodinpine, nisoldipine, nitric oxide (NO), norverapamil and verapamiland combinations, mixtures and/or salts thereof. Verapamil and diltiazemare very effective at inhibiting the AV node, whereas drugs of thenifedipine family have a lesser inhibitory effect on the AV node. Nitricoxide (NO) indirectly promotes calcium channel closure. NO may be usedto inhibit contraction. NO may also be used to inhibit sympatheticoutflow, lessen the release of norepinephrine, cause vasodilation,decrease heart rate and decrease contractility. In the SA node,cholinergic stimulation leads to formation of NO.

[0108] Other drugs, drug formulations and/or drug compositions that maybe used according to this invention may include any naturally occurringor chemically synthesized sodium channel blocker. Sodium channelblockers are also known as sodium channel inhibitors, sodium channelblocking agents, rapid channel blockers or rapid channel inhibitors.Antiarrhythmic agents that inhibit or block the sodium channel are knownas class I antiarrhythmics, examples include, but are not limited to,quinidine and quinidine-like agents, lidocaine and lidocaine-likeagents, tetrodotoxin, encainide, flecainide and combinations, mixturesand/or salts thereof. Therefore, the term “sodium channel blocker”appearing herein may refer to one or more agents that inhibit or blockthe flow of sodium ions across a cell membrane or remove the potentialdifference across a cell membrane. For example, the sodium channel mayalso be totally inhibited by increasing the extracellular potassiumlevels to depolarizing hyperkalemic values, which remove the potentialdifference across the cell membrane. The result is inhibition of cardiaccontraction with cardiac arrest (cardioplegia). The opening of thesodium channel (influx of sodium) is for swift conduction of theelectrical impulse throughout the heart.

[0109] Other drugs, drug formulations and/or drug compositions that maybe used according to this invention may include any naturally occurringor chemically synthesized potassium channel agent. The term “potassiumchannel agent ” appearing herein may refer to one or more agents thatimpact the flow of potassium ions across the cell membrane. There aretwo major types of potassium channels. The first type of channel isvoltage-gated and the second type is ligand-gated.Acetylcholine-activated potassium channels, which are ligand-gatedchannels, open in response to vagal stimulation and the release ofacetylcholine. Opening of the potassium channel causeshyperpolarization, which decreases the rate at which the activationthreshold is reached. Adenosine is one example of a potassium channelopener. Adenosine slows conduction through the AV node. Adenosine, abreakdown product of adenosine triphosphate, inhibits the AV node andatria. In atrial tissue, adenosine causes the shortening of the actionpotential duration and causes hyperpolarization. In the AV node,adenosine has similar effects and also decreases the action potentialamplitude and the rate of increase of the action potential. Adenosine isalso a direct vasodilator by its actions on the adenosine receptor onvascular smooth muscle cells. In addition, adenosine acts as a negativeneuromodulator, thereby inhibiting release of norepinephrine. Class IIIantiarrhythmic agents also known as potassium channel inhibitorslengthen the action potential duration and refractoriness by blockingthe outward potassium channel to prolong the action potential.Amiodarone and d-sotalol are both examples of class III antiarrhythmicagents.

[0110] Potassium is the most common component in cardioplegic solutions.High extracellular potassium levels reduce the membrane restingpotential. Opening of the sodium channel, which normally allows rapidsodium influx during the upstroke of the action potential, is thereforeinactivated because of a reduction in the membrane resting potential.The present invention may be combined with conventional CPB, the inducedasystole as described by this invention may serve as a substitute forconventional cardioplegic arrest. For example, the combination of drugsand vagal stimulation may be used as a cardioplegic agent in a varietyof medical procedures.

[0111] Drugs, drug formulations and/or drug compositions that may beused according to this invention may include any naturally occurring orchemically synthesized (synthetic analogues) ischemia agents. The term“ischemia agent” appearing herein may refer to one or more agents thatprotect one or more organs and/or tissues from ischemic damage. Forexample, delta opioid receptor modulators, mediators, agonists and/orantagonists as disclosed in U.S. Pat. No. 6,103,722 to inventors Schultzand Gross and in U.S. Pat. No. 5,656,420 to inventor Chien have beenused in ischemia protection.

[0112] Although it is desirable to stop the heart for a period of timein order to allow the surgeon to accomplish a required task withoutinterference from heart movement, stopping the heart for prolongedperiods of time may cause damage to various organs and tissues fromischemia or lack of oxygen. Opioid receptor activation on organs andtissues which possess delta opioid receptors has been shown to elicit aprotective effect during periods of ischemia. Delivering an ischemiaagent such as a delta opioid agonist to the patient may protect certainorgans and tissues such as cardiac and/or brain tissue of the patientfrom ischemic damage caused by intermittent periods of cardiac asystole.Examples of delta opioid agonists include, but are not limited to,TAN67(−), DPDPE, BW373U86, DADLE, SB219825, SNC80 and SIOM andcombinations, mixtures and/or salts thereof.

[0113] Drugs, drug formulations and/or drug compositions that may beused during according to this invention may comprise one or more of anynaturally occurring or chemically synthesized beta-blocker, cholinergicagent, cholinesterase inhibitor, calcium channel blocker, sodium channelblocker, potassium channel agent, adenosine, adenosine receptor agonist,adenosine deaminase inhibitor, dipyridamole, monoamine oxidaseinhibitor, digoxin, digitalis, lignocaine, bradykinin agents,serotoninergic agonist, antiarrythmic agents, cardiac glycosides, localanesthetics, P₂-purinoceptor agents, ischemia agents, delta opioidagonists and combinations or mixtures thereof. Digitalis and digoxinboth inhibit the sodium pump. Digitalis is a natural inotrope derivedfrom plant material, while digoxin is a synthesized inotrope.Dipyridamole inhibits adenosine deaminase, which breaks down adenosine.Drugs, drug formulations and/or drug compositions capable of reversiblysuppressing autonomous electrical conduction at the SA and/or AV node,while still allowing the heart to be electrically paced to maintaincardiac output may be used according to this invention.

[0114] In one embodiment, the cardiac asystole produced in accordancewith the present invention is reversible, e.g., chemically such as bythe administration of atropine or by natural forces. Beta-adrenergicstimulation or administration of calcium solutions may be used toreverse the effects of a calcium channel blocker such as verapamil.Agents that promote heart rate and/or contraction may be used in apreferred embodiment of the present invention. For example, dopamine, anatural catecholamine, is known to increase contractility. Positiveinotropes are agents that specifically increase the force of contractionof the heart. Glucagon, a naturally occurring hormone, is known toincrease heart rate and contractility. Glucagon may be used to reversethe effects of a beta-blocker since its effects bypass the betareceptor. Forskolin is known to increase heart rate and contractility.As mentioned earlier, epinephrine and norepinephrine naturally increaseheart rate and contractility. Thyroid hormone, phosphodiesteraseinhibitors and prostacyclin, a prostaglandin, are also known to increaseheart rate and contractility. In addition, methylxanthines are known toprevent adenosine from interacting with its cell receptors.

[0115] Typically, vagal nerve stimulation prevents the heart fromcontracting. This non-contraction must then be followed by periodswithout vagal nerve stimulation during which the heart is allowed tocontract.

[0116] At Block 520, a medical procedure may be performed or begun. Sucha procedure may be for example surgery on the heart. Alternatively, theprocedure may be surgery performed on another organ of the body.

[0117] The term “medical procedure” may mean any one or more medical orsurgical procedures such as, for example cardiac surgery, performed withor without cardiopulmonary bypass (CPB) circuits, heart valve repair,heart valve replacement, MAZE procedures, revascularization procedures,transmyocardial revascularization (TMR) procedures, percutaneousmyocardial revascularization (PMR) procedures, CABG procedures,anastomosis procedures, non-surgical procedures, fluoroscopicprocedures, beating heart surgery, vascular surgery, neurosurgery, brainsurgery, electrophysiology procedures, diagnostic and therapeuticprocedures, ablation procedures, ablation of arrhythmias, endovascularprocedures, treatment of the liver, spleen, heart, lungs, and majorblood vessels, aneurysm repair, imaging procedures of the heart andgreat vessels, CAT scans or MRI procedures, pharmacological therapies,drug delivery procedures, gene therapies, cellular therapies, cancertherapies, radiation therapies, genetic, cellular, tissue and/or organmanipulation or transplantation procedures, coronary angioplastyprocedures, placement or delivery of coated or noncoated stents,atherectomy procedures, atherosclerotic plaque manipulation and/orremoval procedures, procedures where bleeding needs to be preciselycontrolled, procedures that require precise control of cardiac motionand/or bleeding.

[0118] When the medical procedure comprises one or more medical devices,e.g., coated stents, these devices may be coated with one or moreradioactive materials and/or biological agents such as, for example, ananticoagulant agent, an antithrombotic agent, a clotting agent, aplatelet agent, an anti-inflammatory agent, an antibody, an antigen, animmunoglobulin, a defense agent, an enzyme, a hormone, a growth factor,a neurotransmitter, a cytokine, a blood agent, a regulatory agent, atransport agent, a fibrous agent, a protein, a peptide, a proteoglycan,a toxin, an antibiotic agent, an antibacterial agent, an antimicrobialagent, a bacterial agent or component, hyaluronic acid, apolysaccharide, a carbohydrate, a fatty acid, a catalyst, a drug, avitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, anantiviral agent, a viral agent or component, a genetic agent, a ligandand a dye (which acts as a biological ligand). Biological agents may befound in nature (naturally occurring) or may be chemically synthesized.

[0119] The medical procedure may be non-invasive, minimally invasiveand/or invasive. The medical procedure may entail a port-accessapproach, a partially or totally endoscopic approach, a sternotomyapproach or a thoracotomy approach. The medical procedure may includethe use of various mechanical stabilization devices or techniques aswell as various robotic or imaging systems.

[0120] In one method, the heart may be temporarily slowed orintermittently stopped for short periods of time to permit the surgeonto accomplish the required surgical task and yet still allow the heartitself to supply blood circulation to the body. For example, stimulationof the vagus nerve in order to temporarily and intermittently slow orstop the heart is described in U.S. Pat. No. 6,006,134 entitled “Methodand Device for Electronically Controlling the Beating of a Heart UsingVenous Electrical Stimulation of Nerve Fibers,” Dec. 21, 1999, toinventors Hill and Junkman. This patent is assigned to Medtronic, Inc.and is incorporated herein by reference.

[0121] After a time, the medical procedure or one phase of the procedureis completed at 520. After some phase of the medical procedure isperformed, cardiac contractions are allowed to occur (Block 530) Cardiaccontractions may need to occur intermittently during the procedure toensure adequate blood flow. In one embodiment, the stimulation from thenerve stimulation electrodes is stopped or slowed enough to allow theheart to contract. For example, the vagal nerve stimulation is removed,thereby allowing cardiac contractions to occur.

[0122] In another embodiment, the heart may be stimulated to ensure thatcardiac contractions occur (Block 535). For example, cardiac stimulationelectrodes may be used to apply pacing pulses to the heart to encouragethe heart to contract normally. In particular, the pacing pulses may beapplied to the ventricle as is well known in the field. In oneembodiment of the invention, the routine described in FIG. 3 may takeplace at this time to evaluate the stimulation from cardiac stimulationelectrodes until the most satisfactory pairing of stimulating electrodesis determined.

[0123] The present invention permits the heart to be stilled forselected and controllable periods of time in order to permit cardiac orother medical procedure to be performed. While such a period ofstillness is desired, it must not last too long, otherwise insufficientblood and oxygen is delivered to organs. Thus, it is necessary to havethe periods when the heart is beating (Blocks 530, 535).

[0124] If additional medical procedures or additional stages of medicalprocedures need to be performed, the heart may again be stilled usingthe methods of stilling the heart described above. Therefore from Block530 or Block 535, the method may be repeated (Block 540). For example,the heart may again be prevented from contracting by stimulation of thevagal nerve (Block 510). Again, the stimulation electrodes may beevaluated using the routine of the present invention to find the optimalstimulation arrangement. Additional drugs may be delivered or the drugspreviously administered may continue to be administered.

[0125] Additional surgery, additional steps in the medical procedure oradditional medical procedures may again be performed (Block 520) whilethe heart is still. Then, this stage of stillness may be followed byanother stage when the stimulation is removed (Block 530) and the heartis allowed to contract. Again, the heart may be stimulated to encouragecontractions (Block 535). Again, the stimulation electrodes may beevaluated using the routine of the present invention to find the optimalstimulation arrangement.

[0126] This cycle may be repeated until the procedure, such as thesurgery, is completed. After the procedure is completed, step 535 may beperformed until the heart is beating normally. At the procedure's end,one or more of a variety of pharmacological agents or drugs may bedelivered or may continue to be delivered for example to alleviate painor aid in recuperation. Other drugs may be administered for a variety offunctions and purposes as described above.

[0127] For example, a surgical procedure at 520 may require severalstitches to be made by the surgeon. The surgeon may stimulate the vagalnerve at 510 to stop the heart. Then the surgeon may make the firststitch at 520. The surgeon may then reduce or halt stimulation at 530and allow the heart to contract. The surgeon may also pace the heart at535. Then at 540, the surgeon may return to 510 to inhibit contractionsof the heart. At 520, the surgeon will then make the second stitch. Thisprocess may be repeated (the loop designated by 540 may be repeated)until all the required stitches have been made.

[0128]FIG. 9 is a timeline showing the relation of the vagal nervestimulation to the cardiac stimulation in one embodiment of the presentinvention.

[0129] Point 610 indicates a point before the medical procedure hasbegun. At this point 610, both nerve stimulation and cardiac stimulationare off. At point 610, the heart is beating regularly. Then nervestimulation is turned on to inhibit beating of the heart. At point 610,the stimulation electrodes used to stimulate the nerve may be evaluatedaccording to the method of the present invention. During phase 601, thevagal nerve stimulation is on and the cardiac stimulation is off. Thisis the condition of the two types of stimulation at step 520 describedabove.

[0130] Point 611 is a representative point during phase 601. At point611, the contractions of the heart are stilled or substantially slowed.Then during phase 602 the vagal stimulation is turned off (as describedat step 530) and the cardiac stimulation may be turned on (as describedat 535). Point 612 is a representative point during phase 602. At point612, the contractions are allowed and/or may be induced. At point 612,the stimulation electrodes used to stimulation the nerve may beevaluated according to the method of the present invention.

[0131] During phase 603, the vagal nerve stimulation is again turned onand the cardiac stimulation is turned off. Then during phase 604 thevagal stimulation is again turned off and the cardiac stimulation mayagain be turned on. The method of the present invention may be repeatedas necessary until a point is reached, represented by point 615, whenthe necessary medical procedures are completed. At this point 615, nervestimulation is off although cardiac stimulation may be left on in orderto pace the heart to its normal rhythm.

[0132] It will be appreciated by those skilled in the art that while theinvention has been described above in connection with particularembodiments and examples, the invention is not necessarily so limited,and that numerous other embodiments, examples, uses, modifications anddepartures from the embodiments, examples and uses are intended to beencompassed by the claims attached hereto. The entire disclosure of eachpatent and publication cited herein is incorporated by reference, as ifeach such patent or publication were individually incorporated byreference herein.

We claim:
 1. A method of performing a medical procedure, comprising:endotracheal stimulation of a vagal nerve to adjust the beating of aheart to a first condition; performing the medical procedure on anorgan; reducing endotracheal stimulation of the vagal nerve; epicardialstimulation of the heart to adjust the beating of a heart to a secondcondition; reducing epicardial stimulation of the heart; endotrachealstimulation of the nerve a subsequent time in order to re-adjust thebeating of the heart to the first condition; and continuing the medicalprocedure.
 2. The method of claim 1 wherein the endotracheal stimulationis stopped to achieve the second condition.
 3. The method of claim 1wherein the epicardial stimulation is stopped to re-adjust the beatingof the heart to the first condition.
 4. The method of claim I whereinthe first condition is a stopped condition.
 5. The method of claim 1wherein the first condition is a slowed condition.
 6. The method ofclaim I wherein the second condition is a beating condition.
 7. Themethod of claim 1 further comprising: delivering at least one drugduring the medical procedure.
 8. The method of claim 7 wherein the drugis selected from the group consisting of: a beta-blocker, a cholinergicagent, a cholinesterase inhibitor, a calcium channel blocker, a sodiumchannel blocker, a potassium channel agent, adenosine, an adenosinereceptor agonist, an adenosine deaminase inhibitor, dipyridamole, amonoamine oxidase inhibitor, digoxin, digitalis, lignocaine, abradykinin agent, a serotoninergic agonist, an antiarrythmic agent, acardiac glycoside, a local anesthetic, atropine, a calcium solution, anagent that promotes heart rate, an agent that promotes heartcontractions, dopamine, a catecholamine, an inotrope glucagon, ahormone, forskolin, epinephrine, norepinephrine, thyroid hormone, aphosphodiesterase inhibitor, prostacyclin, prostaglandin,methylxanthine, a P₂-purinoceptor agent, an ischemia agent, and a deltaopioid agonist.
 9. The method of claim 8 wherein the drug is naturallyoccurring
 10. The method of claim 8 wherein the drug is chemicallysynthesized.
 11. The method of claim 1 wherein the medical procedure isselected from the group consisting of: surgical procedures, non-surgicalprocedures, endoscopic procedures, fluoroscopic procedures, stentdelivery procedures, aortic aneurysm repairs, cranial aneurysm repairs,delivery of drugs, delivery of biological agents, cardiac surgery withcardiopulmonary bypass circuits, cardiac surgery without cardiopulmonarybypass circuits, brain surgery, cardiograms, heart valve repair, heartvalve replacement, MAZE procedures, transmyocardial revascularization,CABG procedures, beating heart surgery, vascular surgery, neurosurgery,electrophysiology procedures, diagnostic ablation of arrhythmias,therapeutic ablation of arrhythmias, endovascular procedures, treatmentof injuries to the liver, treatment of the spleen, treatment of theheart, treatment of the lungs, treatment of major blood vessels,non-invasive procedures, invasive procedures, and port-accessprocedures.
 12. A system for performing a medical procedure, comprising:an endotracheal nerve stimulator to inhibit beating of the heart; and acardiac stimulator in communication with the endotracheal nervestimulator to stimulate beating of the heart.
 13. The system of claim 12further comprising: drug delivery means for delivering at least one drugduring the medical procedure.
 14. The system of claim 13 wherein thedrug delivery means is selected from the group consisting of: a spray, acream, an ointment, a medicament, a pill, a patch, a catheter, acannula, a needle and syringe, a pump, and an iontophoretic drugdelivery device.
 15. The system of claim 14 wherein the endotrachealnerve stimulator stimulates a parasympathetic nerve fiber.
 16. Thesystem of claim 15 wherein the endotracheal nerve stimulator stimulatesa vagus nerve fiber.
 17. The system of claim 12 wherein the endotrachealnerve stimulator comprises at least one electrode.
 18. The system ofclaim 17 wherein the electrode is selected from the group consisting of:nerve stimulation electrodes, endotracheal electrodes, transcutaneouselectrodes, intracutaneous electrodes, balloon-type electrodes,basket-type electrodes, umbrella-type electrodes, tape-type electrodes,suction-type electrodes, screw-type electrodes, barb-type electrodes,bipolar electrodes, monopolar electrodes, metal electrodes, wireelectrodes, patch electrodes, cuff electrodes, clip electrodes, needleelectrodes and probe electrodes.
 19. The system of claim 12 wherein thecardiac stimulator comprises at least one electrode.
 20. The system ofclaim 19 wherein the electrode is selected from the group consisting of:cardiac stimulation electrodes, clip electrodes, needle electrodes,probe electrodes, pacing electrodes, epicardial electrodes, endocardialelectrodes, patch electrodes, intravascular electrodes, balloon-typeelectrodes, basket-type electrodes, tape-type electrodes, umbrella-typeelectrodes, suction-type electrodes, endoesophageal electrodes,transcutaneous electrodes, intracutaneous electrodes, screw-typeelectrodes, barb-type electrodes, bipolar electrodes, monopolarelectrodes, metal electrodes, wire electrodes and cuff electrodes,. 21.The system of claim 12 further comprising: a respiratory controller forcontrolling respiration.
 22. A device for performing a medical procedurecomprising: a processor; an endotracheal nerve stimulation electrodeoperatively connected to the processor; and a cardiac stimulationelectrode operatively connected to the processor, wherein the processorprocesses output from the nerve stimulation electrode and adjusts outputfrom the cardiac stimulation electrode based on output from the nervestimulation electrode.
 23. The device of claim 22 wherein stimulationfrom the nerve stimulation electrode occurs in an inverse relationshipto stimulation from the cardiac stimulation electrode.
 24. The device ofclaim 22 further comprising: a drug pump for delivering at least onedrug, the drug pump operatively connected to the processor wherein theprocessor adjusts the output of the drug.
 25. The device of claim 22further comprising: a respiratory controller for controllingrespiration, the respiratory controller operatively connected to theprocessor wherein the processor adjusts the output of the respiratorycontroller.
 26. The device of claim 22 wherein endotracheal nervestimulation electrode is arranged on an endotracheal tube.